The primary goal of this work is to understand the physical- chemical basis of cell and tissue excitability. Widely accepted theories of nerve excitability do not explain several important phenomena that we have observed, such as rapid volume and temperature changes that coincide with the time course of excitation. Our findings indicate that swelling and heat production in the superficial protoplasmic layer of nerve axons is a prerequisite for excitatability. Recently, we have investigated the mechanical response of mucosal and granular skin glands in frog to adrenergic stimulation. In this system, we have also observed a pattern of either rapid swelling or rapid shrinking following stimulation. Volume changes occurring in the cytoplasmic gel of the gland cells are considered to be responsible for the observed mechanical response.We have also demonstated that the onset of an action potential is accompanied by a discontinuous volume change in the superficial layer of nerve cells and fibers, and have obtained evidence for the existence of a first-order phase transition (involving volume and temperature changes) in nerve cells, fibers, and synapses associated with this excitation.To understand the physical chemical basis of these temperature and volume changes, we are studying the behavior of synthetic anionic gels under physiological conditions, which share some structural similarities with the axolemma of nerve fibers. - divalent, monovalent, ion exchange, nerve, excitability